1. Field of the Disclosure
The disclosure relates generally to methods for preparing self-aldol condensation products of α,β-unsaturated aldehydes having at least two γ-hydrogens. More specifically, the disclosure describes methods for preparing intermediates useful in the synthesis of flavoring and fragrance compounds from 3-methyl-2-butenal, also known as prenyl aldehyde. In one embodiment, (2E)-5-methyl-2-(1-methylethenyl)-2,4-hexadienal, also known as dehydrolavandulal, (1) is formed, as shown in the following formula:

In another embodiment, (2E,4E)-3,7-dimethyl-2,4,6-octatrienal, also known as dehydrocitral, (2) is formed, as shown in the following formula:

2. Brief Description of Related Technology
The known route to dehydrolavandulal (1) involves the addition of a costly reagent, 2-methyl-3-butyn-2-ol, to prenyl aldehyde under acidic conditions. Subsequent loss of water and rearrangement yields dehydrolavandulal (1), as shown in Scheme 1 (see Fisher et. al., DE 2,212,948). In contrast, the present disclosure provides cost-efficient methods for obtaining dehydrolavandulal (1) from prenyl aldehyde, via amine-catalyzed self-aldol condensation reactions.

For previous routes to dehydrocitral (2) see, e.g., Traas, et. al., Tetrahedron Lett., 1977, 2129-2132. Another method of preparing dehydrocitral (2) involves the coupling of imine derivatives of prenyl aldehyde with prenyl aldehyde under weakly acidic conditions in the presence of a drying agent to obtain dehydrocitral (2), as shown in Scheme 2.

Various products can be obtained from the self-aldol condensation of prenyl aldehyde, with the particular regiochemical outcome of the reaction being determined by the specific reaction conditions. The self-aldol condensation reaction can be controlled, for example, to yield predominantly the γ-1,4-addition product, as shown in Scheme 3. For example, the γ-1,4-condensation product, 4,6,6-trimethyl-1,3-cyclohexadiene-1-carboxaldehyde (3), was exclusively obtained by reaction of the lithium dienolate of prenyl aldehyde with prenyl aldehyde in tetrahydrofuran at −70° C. to −20° C. (Duhamel et al., Tetrahedron Lett., 32:4495 (1991)).

At −10° C. to 0° C. (thermodynamic control), the major condensation product of the potassium dienolate of prenyl aldehyde and prenyl aldehyde is also the γ-1,4-adduct (Cahard et al., Tetrahedron Lett., 39:7093-7096 (1998)). No α-adducts were detected in the crude reaction product. When the same potassium dienolate is reacted with prenyl aldehyde under kinetic control at −78° C., the major product is a mixture of cyclized and dehydrated γ-1,2-addition product, as shown in Scheme 4 (Cahard et al., Tetrahedron Lett., 39:7093-7096 (1998)).

In contrast to the known self-aldol reactions of prenyl aldehyde that form γ-1,4- or γ-1,2-addition products, the present disclosure provides methods for preparing α-1,2-addition products of prenyl aldehyde, as shown in Scheme 5, by use of a weak acid and a catalytic amount of a primary amine at temperatures of 10° C. or greater. The disclosure also provides methods for preparing γ-1,2-adducts of prenyl aldehyde, as shown in Scheme 4, at mild reaction temperatures of 10° C. or greater, instead of −78° C., by use of a weak acid and a catalytic amount of a secondary or tertiary amine.
